This application seeks to bring a relatively new research methodology called Network Science (NS) to the understanding of risk factors for the complex and multi-determined psychopathology of PTSD. Network Science has been applied, in many areas of scientific pursuit, to understand the variables that most contribute to the emergence and persistence of complex phenomena. The methodology of NS enables the determination of whether a given set of variables develops the properties of what has been termed a 'Complex Adaptive System (CAS)'. The essential properties of a CAS include self-organization, self- sustenance, and robustness. A CAS can emerge from natural (e.g. a cell, a disease) or human-made (e.g. the internet, an economy) phenomena. Once a CAS emerges, this complex system of variables becomes highly resistant to external challenge. This perspective has influenced biomedical research in a number of important areas (e.g. cancer, infectious disease, autism) and the term 'Network Medicine'has been coined to describe the application of NS to biomedical research. This application brings together a team with diverse areas of expertise ideally suited to the application of NS to risk factor research for PTSD. Expertise in the following areas is featured in this proposed research: 1) bio-behavioral risk factors for PTSD, 2) genomics of PTSD, 3) computational biology and bioinformatics, 4) child development, and 5) longitudinal research methodology related to PTSD. This team will work together to determine if a complex set of variables related to PTSD may constitute a Complex Adaptive System;and whether the robust properties of such a system lead to the treatment refractory nature of PTSD. Network Science methodology will be applied to 1) the analysis of two compelling longitudinal datasets that contain information ideally suited to understanding the systemic properties of PTSD;and 2) the creation of a Molecular Network Reconstruction of PTSD based on queries of available information on the relationship between PTSD (and related disorders);and the genes and proteins associated with these disorders. If NS reveals a Complex Adaptive System related to traumatic exposure and PTSD, intervention approaches to treat PTSD can be substantially informed by understanding how such a system persists or fails. This application seeks to bring a relatively new research methodology called Network Science (NS) to the understanding of risk factors for the complex and multi-determined psychopathology of PTSD. Network Science has been applied, in many areas of scientific pursuit, to understand the variables that most contribute to the emergence and persistence of complex phenomena. The methodology of NS enables the determination of whether a given set of variables develops the properties of what has been termed a 'Complex Adaptive System (CAS)'. If NS reveals a Complex Adaptive System related to traumatic exposure and PTSD, intervention approaches to treat PTSD can be substantially informed by understanding how such a system persists or fails.